Zhou Jingyi, Ding Qiulan, Chen Yaopeng, Ouyang Qi, Jiang Linlin, Dai Jing, Lu Yeling, Wu Xi, Liang Qian, Wang Hongli, Wang Xuefeng
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
Blood Cells Mol Dis. 2015 Dec;55(4):308-15. doi: 10.1016/j.bcmd.2015.06.002. Epub 2015 Jun 14.
Congenital dysfibrinogenemia (CD) is a rare qualitative disorder of fibrinogen (Fg) with heterogeneous clinical manifestations. We aimed to analyze clinical phenotype and molecular basis of 102 Chinese CD patients and to evaluate the application of thromboelastography (TEG).
Clinical manifestations were recorded and quantified using the consensus ISTH bleeding assessment tool. Kaolin activated TEG and functional Fg TEG were applied in 30 patients. Genetic analysis of Fg genes were performed by direct sequencing.
27.5% patients experienced bleeding, 3.9% had thrombosis and 68.6% were asymptomatic. Females were more prone to experience bleeding (P=0.01). Significant difference (P<0.05) in TEG results were found between patients with hot-spot mutations at AαArg35(16) and γArg301(275), but were not identified between patients with and without bleeding. Normal TEG results were found in patients with mutations at AαArg35(16), AαPro37(18) or AαArg38(19). Six novel mutations were identified, including AαGly33(14)del, AαAsp57(38)Trp60(41)delIVS2+1+2GTdel, AαPhe742(723)Tyr, γAsn334(308)Thr, γGly335(309)Cys and γTrp395(369)Leu.
CD patients have similar clinical manifestations and hot-spot mutations worldwide with no ethnic difference. TEG results could not indicate the bleeding risk in patients, but priority of mutation screening at thrombin cleavage site or polymerization site on Aа chain may be given if TEG results are normal.
先天性纤维蛋白原异常血症（CD）是一种罕见的纤维蛋白原（Fg）定性紊乱疾病，临床表现具有异质性。我们旨在分析102例中国CD患者的临床表型和分子基础，并评估血栓弹力图（TEG）的应用。
使用国际血栓与止血学会（ISTH）共识出血评估工具记录并量化临床表现。对30例患者应用高岭土激活TEG和功能性Fg TEG。通过直接测序对Fg基因进行遗传分析。
27.5%的患者有出血表现，3.9%有血栓形成，68.6%无症状。女性更容易出现出血（P = 0.01）。在Aα链Arg35（16）和γ链Arg301（275）存在热点突变的患者之间，TEG结果存在显著差异（P < 0.05），但有出血和无出血患者之间未发现差异。在Aα链Arg35（16）、Pro37（18）或Arg38（19）发生突变的患者中TEG结果正常。鉴定出6种新突变，包括AαGly33（14）缺失、AαAsp57（38）Trp60（41）缺失IVS2 + 1 + 2GT缺失、AαPhe742（723）Tyr、γAsn334（308）Thr、γGly335（309）Cys和γTrp395（369）Leu。
全球CD患者具有相似的临床表现和热点突变，无种族差异。TEG结果不能提示患者的出血风险，但如果TEG结果正常，可优先对Aα链上凝血酶裂解位点或聚合位点进行突变筛查。
